Characterizing the mitogenic effect of basic fibroblast growth factor in the adult rat striatum

The limited regenerative capacity of the adult central nervous system (CNS) renders it unable to fully recover from injury or disease. Although stem and progenitor cells have been shown to reside throughout the brain, in most regions they exist as quiescent cell populations and do not divide sufficiently to replace damaged or destroyed cells. In an effort to stimulate the proliferative capacity of these multipotent cells, we sought to determine the in vivo response of the adult CNS to an exogenous application of basic fibroblast growth factor (bFGF), a known mitogen to stem and progenitor cells. Specifically, we administered bFGF to the striatum of adult rats at varying concentrations (1, 10, 100, 1,000, or 10,000 ng/mL in saline) so as to establish a dose response curve for bFGF-induced cell proliferation. Forty-eight hours following bFGF administration, animals were injected with 5-bromodeoxyuridine to label dividing cells. Of the doses assessed, we found that 1,000 ng/mL bFGF generated the greatest proliferative response over that observed in animals given a control saline injection. Further, the proliferative response of the striatum to bFGF administration could be enhanced twofold by supplementing this growth factor with heparin sulfate, a factor that facilitates the binding of bFGF to its receptors. By determining the maturational fate of the proliferating cell population, we found that a significant proportion of newly generated cells resulting from bFGF administration differentiated into astrocytes. Collectively, these studies demonstrate the potential of bFGF to promote proliferation in the adult brain, which can be exploited to facilitate cell replacement therapies.